The goal of this project is to learn more about the control of movement in normal humans and in patients with voluntary movement disorders such as Parkinson's disease, cerebellar ataxia, hemiplegia from stroke and dystonia. One major scientific target of the whole laboratory is to understand and possibly influence cortical reorganization in patients with congenital or acquired lesions of the central nervous system. A multi-modality approach (neuroimaging with PET and functional MRI, EEG, and transcranial magnetic stimulation) is being used to determine patterns of long-term reorganization of functional brain topography in individual stroke patients. Analysis of data from patients with subcortical lesions indicated that the reoganization of the cortical activity and excitability patterns depends on the site of the lesion within the internal capsule. Spectral power and coherence analyses of EEG have been used to study learning bimanual movement and making movements at different rates. Synchronization among primary and secondary motor areas of the human brain during movement rate control was studied by EEG coherence measurement. Different sensorimotor integration strategies were observed with auditory-cued repetitive movements of fast and slow movement rates. Event-related coherence focusing on the movement onset revealed the cortical correlates of movement strategy change. The results suggest that the increase of the movement rate is not a linear process. We have examined coherence between the brain and voluntarily active muscle to evaluate how the motor cortex controls the muscle. Frequency-coding of the oscillations was revealed by analyzing the temporal relationships. Separate relationships were seen in the alpha and beta frequency bands. Such analysis has been useful for its physiological insights, but has also helped us in our understanding of the phase feature of coherence analysis. Corticomuscular communication and cortical representation of the process of graded force production was studied by EEG frequency domain analysis. Corticomuscular communication expressed as EEG-EMG coherence was insensitive to the produced force level, while cortical power change in beta band over the contralateralcentral area was linearly correlated with the force level. The results suggest the EEG-EMG coherence as a constant measure of cortico-muscular coupling. Using EEG and PET, we determined that the normal homuncular organization of the primary sensory cortex is degraded in patients with focal dystonia supporting the concept that sensory abnormalities play a pathogenetic role in dystonia. We examined the efficacy of clozapine for generalized and refractory focal dystonias. Objective and subjective measures revealed clinical improvement in symptoms. However, its use was limited by side effcts. We used PET in normal subjects engaged in tasks involving spatial localization of visual and auditory stimuli. Multimodal areas were identified as well as modality specific areas. Our findings suggest that, like in the visual system, the hierarchical organization of the auditory system extends beyond the primary auditory cortex to include areas in the posterior parietal and prefrontal regions. These results may explain the dissociation of the visual and auditory spatial deficits reported for patients with lesions involving these regions. We have studied a group of patients with Friedreich's ataxia by means of MRI in order to detect differences in the iron content of the dentate nucleus. The preliminary results showed a clear trend towards increased iron in the cerebellum in young patients with Friedreich's ataxia but not in more advanced older patients.